rs11166983

chr8-140547987-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012154.5(AGO2):c.1589-360T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,102 control chromosomes in the GnomAD database, including 13,112 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13112 hom., cov: 32)
• Consequence: AGO2 NM_012154.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

Genes affected

AGO2 (HGNC:3263): (argonaute RISC catalytic component 2) This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, and contains a PAZ domain and a PIWI domain. It may interact with dicer1 and play a role in short-interfering-RNA-mediated gene silencing. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGO2	NM_012154.5	c.1589-360T>C		intron_variant		ENST00000220592.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGO2	ENST00000220592.10	c.1589-360T>C		intron_variant		1	NM_012154.5	P1
AGO2	ENST00000519980.5	c.1589-360T>C		intron_variant		1
AGO2	ENST00000523609.5	c.*1174-360T>C		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62289 AN: 151984 Hom.: 13098 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.394

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.410 AC: 62336 AN: 152102 Hom.: 13112 Cov.: 32 AF XY: 0.414 AC XY: 30746 AN XY: 74350

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.396

Alfa AF: 0.392 Hom.: 1482

Bravo AF: 0.420

Asia WGS AF: 0.529 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.3
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11166983; hg19: chr8-141558086;